Interleukin 3 Stimulation Enhances Tyrosine Phosphorylation and Proliferative Activity of Human Fetal Thymocytes and Leukemic T-cell Precursors at Multiple Developmental Stages of T-Cell Ontogeny

Abstract

117 Downloaded by [University of Otago] at 12:42 27 July 2015 118 F. M. UCKUN et a/.thymic microenvironment. Stimulation of fetal thymocytes with rhIL-3 resulted in enhanced tyrosine phosphorylation of 8 distinct cellular substrates with molecular weights of 44 kDa, 55 kDa, 60 kDa, 69 kDa, 98 kDa, 123 kDa, 150 kDa and 190 kDa, but it did not result in stimulation of phosphoinositide turnover and increased Ins-l,4,5-P3 production. The induction of tyrosine phosphorylation by rhlL-3 was augmented by further crosslinking surface bound IL-3 molecules with an anti-IL-3 antibody and it was abrogated by the tyrosine kinase inhibitor genistein. The ligation of the CD45 protein tyrosine phosphatase markedly suppressed the tyrosine phosphorylation of specific substrates induced by IL-3 stimulation. Thus, the mitogenic transmembrane signal triggered by the engagement of the IL-3 R on human T-cell precursors is linked to a functional protein tyrosine kinase (PTK)/protein tyrosine phosphatase (PTP) regulatory pathway. Taken together, these results indicate that IL-3 may have an important growth regulatory role in early stages of human T-cell ontogeny. KEY WORDS:Interleukin 3 Tyrosine phosphorylation proliferative activity foetal lymphocytes leukemic T-precursors T-cell ontogeny